RABSEL

Among autoimmune diseases, rheumatoid arthritis (RA) is the most frequent, affecting 0.3-1% of the population worldwide. This disease evolves by outbreaks because of inflammation of the synovial membrane of the joints, resulting in joint destruction and pain. RA is not a curable disease; there is an urgent need to develop new treatments. Macrophages are important in the pathogenesis of RA, as activated macrophages contribute considerably to inflammation and joint destruction by releasing cytokines, chemokines, digestive enzymes, prostaglandins and reactive oxygen species, which exacerbate the damages to the normal tissues. This project proposes to develop an innovative treatment by combining targeted delivery of methotrexate (MTX) treatment by a carrier (carbon nanotubes, CNTs) with the selective elimination of the inflammatory cells present in the arthritic joints, including the activated macrophages, thus resulting in a drastic reduction of inflammation and other symptoms of RA. This treatment is based on near-infrared (NIR) light-triggered photothermal therapy through the generation of localized heat in the inflammatory cells in the arthritic joints via phagocytosis of a photothermal agent (CNTs), leading to the specific death of these cells. The CNTs will be coated with the cell membrane of macrophages to target specifically and accumulate in the inflamed synovium, where they will be internalized into the phagocytic inflammatory cells. A local NIR light irradiation will induce the selective thermal elimination of these cells. The use of CNTs a delivery system will allow a high concentration of MTX in the joints, resulting in less side effects compared to administration of free MTX. Our therapeutic biomimetic strategy is versatile and could be applied to the treatment of other diseases, as activated macrophages contribute conspicuously to many other inflammatory and autoimmune diseases, like systemic lupus erythematosus, Sjögren's syndrome and Behcet's disease.